Delving into the Latest Updates on TMX-202 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

TLR7

Action

agonists

Mechanism

TLR7 agonists(Toll like receptor 7 agonists)

Therapeutic Areas

NeoplasmsInfectious DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication

Bladder CancerCondylomata AcuminataSkin Neoplasms

Inactive Indication-

Originator Organization

University of California San Diego

Active Organization

University of California San Diego

Inactive Organization

Telormedix SA

License Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC45H73N6O12P

InChIKeyDFFGHPOFYMBXJP-DIPNUNPCSA-N

CAS Registry1346110-99-3

Four groups of 14 rats received an instillation with isogenic AY-27 tumor cells on day 0, starting tumor development. On day 2 and 5, the rats were treated with an intravesical instillation of TMX-101 0.1%, TMX-202 0.38%, vehicle solution or NaCl. On day 12 the rats were sacrificed and the bladders were evaluated histopathologically.

RESULTS:

No signs of toxicity were seen. The number of tumor-positive rats was 11 of 14 (79%) in the vehicle control group and in the NaCl control group, versus 9 of 14 (64%) in the TMX-101-treated group, and 8 of 14 (57%) in the TMX-20-treated group. The difference between tumor-bearing rats in the treated and control groups was not significant (p = 0.12). Bladder weight was significantly lower for TMX-202-treated rats compared to vehicle (p = 0.005).

CONCLUSIONS:

TMX-101 and TMX-202 are TLR-7 agonists with antitumor activity. Treatment with TMX-101 and TMX-202 resulted in less tumor-bearing rats compared to vehicle or saline control groups, although not statistically significant. In this aggressive bladder cancer model, a lower number of tumor-positive rats after treatment with TLR-7 agonists indicates activity for the treatment of non-muscle invasive bladder cancer.

01 May 2018·Urologic oncologyQ3 · MEDICINE

Pharmacokinetics and pharmacodynamics of intravesical and intravenous TMX-101 and TMX-202 in a F344 rat model

Q3 · MEDICINE

Article

Author: Oosterwijk, Egbert ; Witjes, Johannes Alfred ; Hulsbergen-van de Kaa, Christina A ; Maj, Roberto ; Falke, Johannes

OBJECTIVES:

To evaluate and compare the pharmacokinetic and pharmacodynamic properties of 2 investigational Toll-like receptor 7 agonists, TMX-101, and TMX-202 after intravenous and intravesical administration in a rat model. TLR-7 agonists are successfully used as topical treatment for various (pre)malignant skin lesions and are now under investigation as intravesical therapy for non-muscle-invasive bladder cancer.

METHODS:

Rats received an intravesical instillation with TMX-101, TMX-202, or vehicle. Additionally 2 groups of rats received an intravenous injection with TMX-101 or TMX-202. Blood sampling was performed at different time points, including pre-exposure and postexposure to determine the plasma concentrations of study drugs for pharmacokinetic and pharmacodynamic analyses and to determine the plasma concentrations of cytokines (IL-2, IL-6, and TNF-α).

RESULTS:

We observed no signs of toxicity after intravesical or intravenous administration. There was a limited dose dependent systemic uptake of TMX-101 and TMX-202 after intravesical administration. The systemic uptake of TMX-202 after intravesical instillation was 25 times lower compared to TMX-101.

CONCLUSIONS:

This in vivo study confirms the safety of intravesical TMX-101 and TMX-202 administration, with TMX-202 showing lower systemic uptake. TMX-202 has a larger molecule-mass compared to TMX-101, and it may therefore have a favorable safety profile when treating patients with non-muscle-invasive bladder cancer intravesically.

01 Apr 2017·Acta biomaterialiaQ1 · ENGINEERING & TECHNOLOGY

Delivery of TLR7 agonist to monocytes and dendritic cells by DCIR targeted liposomes induces robust production of anti-cancer cytokines

Q1 · ENGINEERING & TECHNOLOGY

Article

Author: Zucker, Daniel ; Laursen, Janne M ; Jensen, Simon S ; Andresen, Thomas L ; Brix, Susanne ; Klauber, Thomas C B

STATEMENT OF SIGNIFICANCE:

Cancer immunotherapy is a powerful new tool in the oncologist's therapeutic arsenal, with our increased knowledge of anti-tumor immunity providing many new targets for intervention. Monocytes and dendritic cells (DCs) are attractive targets for enhancing the anti-tumor immune response, but systemic delivery of immunomodulators has proven to be associated with a high risk of fatal adverse events due to the systemic activation of the immune system. We address this important obstacle by targeting the delivery of an immunomodulator, a Toll-like receptor agonist, to DCs and monocytes in the bloodstream. We thus focus the activation, potentially avoiding the above-mentioned adverse effects, and demonstrate greatly increased ability of the agonist to induce secretion of anti-cancer cytokines.

100 Deals associated with TMX-202

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bladder Cancer	Phase 1	-	Telormedix SA	-
Bladder Cancer	Phase 1	-	University of California San Diego	-
Condylomata Acuminata	Phase 1	-	University of California San Diego	-
Condylomata Acuminata	Phase 1	-	Telormedix SA	-
Skin Neoplasms	Phase 1	-	Telormedix SA	-
Skin Neoplasms	Phase 1	-	University of California San Diego	-